Comparative promoter analysis allows de novo identification of specialized cell junction-associated proteins

Clemens D Cohen, Andreas Klingenhoff, Anissa Boucherot, Almut Nitsche, Anna Henger, Bodo Brunner, Holger Schmid, Monika Merkle, Moin A Saleem, Klaus-Peter Koller, Thomas Werner, Hermann-Josef Gröne, Peter J Nelson, Matthias Kretzler

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    86 Citations (Scopus)

    Abstract

    Shared transcription factor binding sites that are conserved in distance and orientation help control the expression of gene products that act together in the same biological context. New bioinformatics approaches allow the rapid characterization of shared promoter structures and can be used to find novel interacting molecules. Here, these principles are demonstrated by using molecules linked to the unique functional unit of the glomerular slit diaphragm. An evolutionarily conserved promoter model was generated by comparative genomics in the proximal promoter regions of the slit diaphragm-associated molecule nephrin. Phylogenetic promoter fingerprints of known elements of the slit diaphragm complex identified the nephrin model in the promoter region of zonula occludens-1 (ZO-1). Genome-wide scans using this promoter model effectively predicted a previously unrecognized slit diaphragm molecule, cadherin-5. Nephrin, ZO-1, and cadherin-5 mRNA showed stringent coexpression across a diverse set of human glomerular diseases. Comparative promoter analysis can identify regulatory pathways at work in tissue homeostasis and disease processes.

    Original languageEnglish
    Pages (from-to)5682-7
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume103
    Issue number15
    DOIs
    Publication statusPublished - 11 Apr 2006

    Keywords

    • Animals
    • Antigens, CD
    • Cadherins
    • Conserved Sequence
    • Evolution, Molecular
    • Gene Expression Regulation
    • Humans
    • Intercellular Junctions
    • Membrane Proteins
    • Mice
    • Models, Genetic
    • Phosphoproteins
    • Podocytes
    • Promoter Regions, Genetic
    • Rats
    • Transcription Factors
    • Vertebrates
    • Zonula Occludens-1 Protein

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